title: Coffin-Siris syndrome is a SWI/SNF complex disorder.
abstract: Coffin-Siris syndrome (CSS) is a congenital disorder characterized by intellectual disability, growth deficiency, microcephaly, coarse facial features, and hypoplastic or absent fifth fingernails and/or toenails. We previously reported that five genes are mutated in CSS, all of which encode subunits of the switch/sucrose non-fermenting (SWI/SNF) ATP-dependent chromatin-remodeling complex: SMARCB1, SMARCA4, SMARCE1, ARID1A, and ARID1B. In this study, we examined 49 newly recruited CSS-suspected patients, and re-examined three patients who did not show any mutations (using high-resolution melting analysis) in the previous study, by whole-exome sequencing or targeted resequencing. We found that SMARCB1, SMARCA4, or ARID1B were mutated in 20 patients. By examining available parental samples, we ascertained that 17 occurred de novo. All mutations in SMARCB1 and SMARCA4 were non-truncating (missense or in-frame deletion) whereas those in ARID1B were all truncating (nonsense or frameshift deletion/insertion) in this study as in our previous study. Our data further support that CSS is a SWI/SNF complex disorder.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsurusaki
authors.forename: N
authors.initials: N
authors.lastname: Okamoto
authors.forename: H
authors.initials: H
authors.lastname: Ohashi
authors.forename: S
authors.initials: S
authors.lastname: Mizuno
authors.forename: N
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Makita
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: B
authors.initials: B
authors.lastname: Isidor
authors.forename: J
authors.initials: J
authors.lastname: Perrier
authors.forename: S
authors.initials: S
authors.lastname: Aggarwal
authors.forename: A B
authors.initials: AB
authors.lastname: Dalal
authors.forename: A
authors.initials: A
authors.lastname: Al-Kindy
authors.forename: J
authors.initials: J
authors.lastname: Liebelt
authors.forename: D
authors.initials: D
authors.lastname: Mowat
authors.forename: M
authors.initials: M
authors.lastname: Nakashima
authors.forename: H
authors.initials: H
authors.lastname: Saitsu
authors.forename: N
authors.initials: N
authors.lastname: Miyake
authors.forename: N
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D059472:Exome; D005145:Face / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008844:Micrognathism / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009333:Neck / Q000002:abnormalities* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D000071796:SMARCB1 Protein; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C497837:ARID1B protein, human; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases
keywords: ARID1B; Coffin-Siris syndrome; SMARCA4; SMARCB1; SWI/SNF ATP-dependent chromatin-remodeling complex